Influenza (called “flu” for short below) is an acute respiratory disease caused by influenza virus (called “flu virus” for short below). It spreads through the respiratory, has relative high infection rates and several of them may cause severe morbidity and mortality. The spreading of influenza virus may be divided into several classes blow according with the characters thereof.
1. Seasonal influenza. Seasonal influenza is the most common form of influenza which breaks out annually, and in autumn or winter the outbreak is often in large scale. As estimated by the World Health Organization (WHO), every year about 600 million people are infected, and 3-5 million suffer from severe conditions and result in 250-500 thousand cases of deaths. In developed countries with abundant medical resource most cases of death occur in the aged population. In the United States it is estimated that every year around 36,000 people die of seasonal influenza, and about 90% are aged above 65 (Thompson et al. Am J Public Health. 2009). Currently the marketed vaccines against seasonal influenza include inactivated virus vaccines and split vaccine for intramuscular injection, and live attenuated vaccines for mucosal vaccination, which all compose of three different types of influenza virus antigens, namely H1N1, H3N2 and Flu B.
2. Influenza pandemic. Influenza pandemic is caused by the antigen conversion due to the rearrangement of influenza virus genes. Such influenza pandemic shows great harm to the society, because human seldom develops immunity against such mutation in such big segment in the genome. In the last century there were three outbreaks of such influenza pandemic, and each outbreak resulted in a great number of infections and deaths, and caused great loss to the economics as well as to the society. As estimated the “Spanish Influenza” (Span flu), one of the most severe natural calamities in the history, happened during 1918-1920, infected about 500 million people (one third of the world population), and killed 40-50 million which was 3% of the world population then. Thereafter, “Asian influenza” and “Hongkong influenza” took place in 1957 and 1968, and also caused millions of cases of death. With the development of the society, the communications between countries and districts has been becoming more and more convenient and frequent, which has also facilitated the spreading of influenza pandemic. WHO believes in the past it takes 6-9 months for an influenza pandemic to spread over the world but now only 3 months is needed. It is estimated that in developed counties, the next influenza pandemic will bring 130 million outpatients, 2 million inpatients, and 650 thousand deaths. In developing countries the influence would be more severe, and there would even be millions of deaths. Therefore, such influenza pandemic would be great risks to global public health. The H1N1 influenza in 2009 has also been paid great attention by WHO and different national health authorities because it shows characters of an influenza pandemic.
3. Bird Influenza. This infection is caused by mutant bird virus. Although no outbreak has been observed in human population, the extremely high fatality rate has brought great risks to human health. Also, such highly pathogenic avian influenza could hardly get controlled because the wild hosts thereof migrate continuously, so it has brought new challenges to global public health. WHO has reported 492 cases up to Mar. 30, 2010, and there have been 291 deaths (the data comes from the website of the Chinese Center of Disease Control Office of Emergency.
The public health offices of different countries has made efforts to defend against such danger, and WHO has set up a global monitoring network and hopes alarms could be made according to such monitoring. Until now, the most effective way to control spreading of infectious diseases is vaccine. Especially in influenza virus, influenza vaccine immunization is the most effective means to prevent and control the spreading of influenza virus. Although the three types of influenza spreading are correspond to different marketed vaccines, current vaccines only protect the object from being infected by the influenza viruses which are identical or similar to the vaccine strain, and are unlikely to overcome the mutation of viruses to prevent the infection caused by multiple or different influenza viruses from vaccine strains. Therefore, the candidate vaccine strains for seasonal influenza viruses in each influenza season would be reappraised by WHO according to the spreading trend, and the vaccine strains would be renewed every year. The vaccine strains selected may be not matched with the seasonal spreading virus strains, and there are risks in the effect of the vaccine.
As indicated by reported data, influenza virus hemagglutinin (HA) protein is a protective antigen, which protects the host by inducing neutralizing antibody (nAb). Therefore, the influenza vaccines are evaluated on the HA content, and the effect for the vaccine is evaluated by the titer of hemagglutination inhibition antibodies. As well known by people skilled in the art, HA is the protein with most mutations in A-flu. Until now there has been 16 subtypes of HA discovered, and the antigenicity between the HA antigens are not the same. Although the protection related epitopes are mostly found in HA, and current vaccines may induce antibodies with high titer, however, the epitopes with high immunogenicity changes all the time. A vaccine is only effective against the virus strain it is identical to or the similar strains, and does not show broad protection ability against other strains or new strains. Essentially, the current vaccine technology does not overcome the mutation among the virus strains to archive a broad, cross protection.
Also it is expected to obtain a vaccine with broad protection ability, and retain strong protection against Influenza A, subtype H1. In 2009, H1N1 influenza has spread around the world and has caused many deaths. The protection ability against H1 influenza is thus an important scale for a vaccine.